Identification of mutations in AP4S1/SPG52 through next generation sequencing in three families.
Eur J Neurol
; 23(10): 1580-7, 2016 10.
Article
em En
| MEDLINE
| ID: mdl-27444738
ABSTRACT
BACKGROUND AND PURPOSE:
The term hereditary spastic paraplegia (HSP) covers a spectrum of genetically heterogeneous disorders in which lower limb spasticity is the common clinical feature. Many patients with childhood-onset HSP are mistakenly diagnosed with cerebral palsy (CP).METHODS:
A group of as yet molecularly undiagnosed HSP patients were analyzed using SpastoPlex, a customized target re-sequencing panel able to investigate the coding regions of 72 genes linked to HSP, spastic ataxias or related motor diseases.RESULTS:
Our investigations identified loss-of-function mutations in AP4S1/SPG52 in four children (three families) who had previously received a diagnosis of diplegic/quadriplegic CP. The patients presented spastic paraparesis, mild facial dysmorphisms, moderate-to-severe intellectual disability and severe speech delay. Two patients manifested febrile seizures and childhood-onset focal seizures. In all the patients, brain magnetic resonance imaging (MRI) showed a peculiar hypoplastic posterior corpus callosum, often associated with ventriculomegaly, white matter loss and cerebral atrophy.CONCLUSION:
Adaptor protein 4 (AP-4) deficiency disorders should be suspected in children with spastic paraparesis, cognitive deficit and absent speech accompanied by suggestive MRI features. Seizures might be amongst the clinical manifestations of the syndrome.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Paraplegia Espástica Hereditária
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Complexo 4 de Proteínas Adaptadoras
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adolescent
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Eur J Neurol
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Itália